The non-protein amino acid β-N-methylamino-L-alanine (BMAA) is produced by diverse taxa of cyanobacteria (Cox et al. (2005) Proc Natl Acad Sci USA 102: 5074-5078) and has been shown to have neuroexcitatory and neurotoxic effects when administered in vivo and in vitro under various experimental conditions. Because BMAA can be found in flour made from cycad seeds, BMAA has been considered a candidate neurotoxin associated with a unique neurological disease identified decades ago among the Chamorro people of Guam, known as amyotrophic lateral sclerosis-Parkinsonism dementia complex of Guam (ALS-PDC) because of the combination of symptoms having clinical similarity to features of amyotrophic lateral sclerosis (ALS), Parkinsonism, and dementias, where occurrence of the disease has been linked with a diet that includes BMAA-containing cycad flour. (inter alia, Spencer et al. (1987) Science 237:517-522; Kisby et al. (1992) Neurodegeneration 1:73-82). Biomagnification of BMAA in food chains has been demonstrated, e.g. in Guam, where BMAA produced by cyanobacterial symbionts in cycad roots is taken up by the cycad host and accumulated in structures such as the seed sarcotesta and seed gametophyte that are eaten by flying foxes (bats) or people that further accumulate BMAA in their tissues, with a dramatic biomagnification seen when flying foxes (bats) with high accumulated levels of BMAA are eaten by people. (inter alia, Bannack et al. (2003) Neurology 61387-389; Cox et al. (2002) Neurology 58: 956-959; Cox et al. (2003) Proc Natl Acad Sci USA 100:13380-13383).
Recently, BMAA has since been detected in tissues of subjects who have not eaten cycads or flying foxes, where some subjects with detectable levels of BMAA had clinical diagnoses (based on symptoms) or confirmed diagnoses (e.g., based on autopsy of brain tissue) of neurological disorders such as Alzheimer's disease, ALS, and progressive supranuclear palsy (PSP), while other subjects with detectable levels of BMAA were asymptomatic for neurological disorders. (Cox et al. (2003) Proc Natl Acad Sci USA 100:13380-1338; Murch et al. (2004) Proc Natl Acad Sci USA 101: 12228-12231; Murch et al. (2004) Acta Neurol Scand 110:267-269; U.S. Pat. No. 7,256,002; US Publication No. 20070254315; US Publication No. 20070292893)
Chromatographic methods for analyzing tissue samples and environmental samples for neurotoxic amino acids such as BMAA, by high performance liquid chromatography (HPLC) or HPLC-mass spectroscopy (HPLC-MS) analysis of tissue samples and/or environmental samples is disclosed (Cox et al. (2003) Proc Natl Acad Sci USA 100:13380-1338; Murch et al. (2004) Proc Natl Acad Sci USA 101: 12228-12231; Murch et al. (2004) Acta Neurol Scand 110:267-269; U.S. Pat. No. 7,256,002; US Publication No. 20070254315)